Estudo das alterações renais e vasculares promovidas pelo veneno total de Bothrops lutzi

Abstract

Toxinology is a science dedicated to the study of toxins derived from microorganisms, plants and animals; as it is closely related to health biotechnology, it allows to reveal the mechanisms of action of toxins, to develop pharmacological tools, new treatment protocols and to improve better prognoses. The study of toxins of new species of snakes such as Bothrops lutzi is Included in this context. The aim of this study was to evaluate the renal and vascular changes promoted by the snake B. lutzi venom. Studies with isolated rat kidneys were performed in a perfusion system that allows to evaluate possible changes in renal parameters; further studies with renal tubular epithelial cells of dog (MDCK), permitted to observe the possible expression of pro-apoptotic genes. We studied also the possible vascular changes induced by this venom in aortic rings and mesenteric vascular beds. The results showed that the B. lutzi venom of (BLV) induced significant changes in all renal parameters studied, mainly the reduction of perfusion pressure (PPcontrol somin = 108.69±5.08mmHg vs. PPBLV 1.0pg/mL somin = 73.55±2.79mmHg) and renal vascular resistance (RVRcontrol somin = 5.32±0.57mmHg. mL-1. g-1. min-1 vs. RVRBLv 1.0pg/mL somin = 3.39±0.30mmHg. mL 1. g-1. min-1), while increasing urinary flow (UFcontroi 120min = 0.160±0.020 mL.g-1. min-1VS. UFBLV 10.0pg/mL 120min = 0.981±0.103mL.g-1. min-1) and glomerular filtration rate (GFR conntrol 120min = 0.697±0.084 mL.g-1. min-1 vs. GFRBLv 10.0Ng/mL 12omin = 3.152±0.342mL.g-1. min-1) in at least one of the concentrations studied. The most relevant fact is that this poison is highly toxic to the renal tubules, and this fact was demonstrated by the decrease of the percentage of transport of sodium (Na +), potassium (K +) and chloride (Cl-) in all concentrations, regardless of PP reduction. These parameters were reduced by at least 10.0% when compared to controls. Tubular damages were also observed by histological analysis (evidence of apoptosis/direct cellular damage); reduction of MDCK cell viability was noticed up to 92.34% (BLV 100.0pg/mL); the expression of pro-apoptotic genes CASP- 3 and CASP-8 was not observed in this protocol (CASP-3control =1.09±0.08 vs. CASP-3BLV=1.01±0.08; CASP-8control= 1.04±0.05 vs. CASP-8BLv=0.93±0.06). PP reduction seems to be related to the relaxation of renal vessels of which vasodilatory effects were observed in aortic rings, with relaxation of 23.89% (BLV 20.0pg/mL), though we have not observed such effects in the mesenteric vascular bed. Thus, B. lutzi venom seems to affect mainly renal tubules, independently from the vascular actions; in addition, cellular death has occurred regardless of nonexpression of pro-apoptotic genes.